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1.
Adv Exp Med Biol ; 1169: 1-30, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487016

RESUMO

In this chapter, heterogeneity is explored in the context of the ventricular-subventricular zone, the largest stem cell niche in the mammalian brain. This niche generates up to 10,000 new neurons daily in adult mice and extends over a large spatial area with dorso-ventral and medio-lateral subdivisions. The stem cells of the ventricular-subventricular zone can be subdivided by their anatomical position and transcriptional profile, and the stem cell lineage can also be further subdivided into stages of pre- and post-natal quiescence and activation. Beyond the stem cells proper, additional differences exist in their interactions with other cellular constituents of the niche, including neurons, vasculature, and cerebrospinal fluid. These variations in stem cell potential and local interactions are discussed, as well as unanswered questions within this system.


Assuntos
Encéfalo , Ventrículos Laterais , Células-Tronco Neurais , Nicho de Células-Tronco , Animais , Encéfalo/citologia , Linhagem da Célula , Ventrículos Laterais/citologia , Camundongos , Células-Tronco Neurais/citologia , Neurônios/citologia , Nicho de Células-Tronco/fisiologia
2.
Bratisl Lek Listy ; 120(9): 650-657, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475548

RESUMO

In this contribution we present graph theoretical approach to image processing focus on biological data. We use the graph cut algorithms and extend them for obtaining segmentation of biological data. We deal with tumor brain cells and rats brain to show the existence and presence of inflammatory molecules. We introduce a completely new method for filtering of data (Tab. 3, Schema 4, Fig. 7, Ref. 13). Keywords: graph cuts, segmentation, tumore analyses of cells, computer morphometry.


Assuntos
Algoritmos , Neoplasias Encefálicas/patologia , Processamento de Imagem Assistida por Computador , Modelos Teóricos , Animais , Encéfalo/citologia , Ratos
3.
Nat Neurosci ; 22(10): 1536-1543, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31477899

RESUMO

Activity-dependent synaptic plasticity has since long been proposed to represent the subcellular substrate of learning and memory, one of the most important behavioral processes through which we adapt to our environment. Despite the undisputed importance of synaptic plasticity for brain function, its exact contribution to learning processes in the context of cellular and connectivity modifications remains obscure. Causally bridging synaptic and behavioral modifications indeed remains limited by the available tools to measure and control synaptic strength and plasticity in vivo under behaviorally relevant conditions. After a brief summary of the current state of knowledge of the links between synaptic plasticity and learning, we will review and discuss the available and desired tools to progress in this endeavor.


Assuntos
Aprendizagem/fisiologia , Plasticidade Neuronal/fisiologia , Animais , Encéfalo/citologia , Encéfalo/fisiologia , Humanos , Vias Neurais/citologia , Vias Neurais/fisiologia
4.
Nat Neurosci ; 22(10): 1731-1742, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31501572

RESUMO

Mitochondria vary in morphology and function in different tissues; however, little is known about their molecular diversity among cell types. Here we engineered MitoTag mice, which express a Cre recombinase-dependent green fluorescent protein targeted to the outer mitochondrial membrane, and developed an isolation approach to profile tagged mitochondria from defined cell types. We determined the mitochondrial proteome of the three major cerebellar cell types (Purkinje cells, granule cells and astrocytes) and identified hundreds of mitochondrial proteins that are differentially regulated. Thus, we provide markers of cell-type-specific mitochondria for the healthy and diseased mouse and human central nervous systems, including in amyotrophic lateral sclerosis and Alzheimer's disease. Based on proteomic predictions, we demonstrate that astrocytic mitochondria metabolize long-chain fatty acids more efficiently than neuronal mitochondria. We also characterize cell-type differences in mitochondrial calcium buffering via the mitochondrial calcium uniporter (Mcu) and identify regulator of microtubule dynamics protein 3 (Rmdn3) as a determinant of endoplasmic reticulum-mitochondria proximity in Purkinje cells. Our approach enables exploring mitochondrial diversity in many in vivo contexts.


Assuntos
Encéfalo/citologia , Mitocôndrias/metabolismo , Neurônios/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Esclerose Amiotrófica Lateral/metabolismo , Esclerose Amiotrófica Lateral/patologia , Animais , Astrócitos/metabolismo , Sinalização do Cálcio/genética , Sinalização do Cálcio/fisiologia , Células Cultivadas , Cerebelo/citologia , Ácidos Graxos/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Membranas Mitocondriais/metabolismo , Proteômica , Células de Purkinje/metabolismo
5.
Nat Neurosci ; 22(10): 1696-1708, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31551601

RESUMO

The mammalian brain is complex, with multiple cell types performing a variety of diverse functions, but exactly how each cell type is affected in aging remains largely unknown. Here we performed a single-cell transcriptomic analysis of young and old mouse brains. We provide comprehensive datasets of aging-related genes, pathways and ligand-receptor interactions in nearly all brain cell types. Our analysis identified gene signatures that vary in a coordinated manner across cell types and gene sets that are regulated in a cell-type specific manner, even at times in opposite directions. These data reveal that aging, rather than inducing a universal program, drives a distinct transcriptional course in each cell population, and they highlight key molecular processes, including ribosome biogenesis, underlying brain aging. Overall, these large-scale datasets (accessible online at https://portals.broadinstitute.org/single_cell/study/aging-mouse-brain ) provide a resource for the neuroscience community that will facilitate additional discoveries directed towards understanding and modifying the aging process.


Assuntos
Envelhecimento/genética , Encéfalo/crescimento & desenvolvimento , Neurônios/fisiologia , Análise de Célula Única , Transcriptoma/genética , Animais , Encéfalo/citologia , Comunicação Celular/genética , Linhagem da Célula/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ribossomos/genética
6.
Chem Commun (Camb) ; 55(67): 9955-9958, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31364619

RESUMO

A silver nanocluster-based ratiometric fluorescent nanosensor was developed for the determination of ATP in the cerebrospinal fluid of a mouse brain. Using this useful tool with good stability and high selectivity as well as a wide linear detection range, it was found that the ATP concentration in a mouse brain with Alzheimer's disease was 2300-fold higher than that in a normal one.


Assuntos
Trifosfato de Adenosina/líquido cefalorraquidiano , Química Encefálica , DNA/química , Corantes Fluorescentes/química , Nanopartículas Metálicas/química , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/citologia , Encéfalo/patologia , Córtex Cerebral/química , Hipocampo/química , Camundongos , Conformação de Ácido Nucleico , Prata/química , Espectrometria de Fluorescência/métodos
8.
Gene ; 717: 143998, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31381951

RESUMO

Eid1 is a member of the EID protein family, which regulates differentiation, transcription and acetyltransferase activity. Accumulating evidence suggests that Eid1 is relevant to neurological disorder, but the main function of Eid1 is still unclear, especially in the brain. To better understand this issue, we generated Eid1-knockout (Eid1-KO) mice and profiled its gene expression changes in the brain by RNA sequencing. This study identified 2531 genes differentially expressed in Eid1-KO mice compared with the wild-type, then qRT-PCR verification demonstrated that the transcriptomic data are reliable. By protein-protein interaction cluster analysis, 'regulation of cell proliferation' were unexpectedly discovered as important Eid1 functions. We then isolated neural progenitor cells (NPCs) and showed that the number of neurospheres and the proliferation rate of Eid1-KO NPCs were obviously lower than that in the control group, furthermore, CCK-8 and immunofluorescence assay clearly demonstrated that the Eid1-KO NPCs showed significantly less cell proliferation than the control group. To the best of our knowledge, this is the first comprehensive report of the Eid1-KO transcriptome of mice brain. Our analysis and experimental data provide a foundation for further studies on understanding function of Eid1 in the brain.


Assuntos
Encéfalo/citologia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Animais , Encéfalo/embriologia , Encéfalo/fisiologia , Proliferação de Células/genética , Feminino , Perfilação da Expressão Gênica , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células-Tronco Neurais/citologia , Células-Tronco Neurais/fisiologia , Gravidez , Mapas de Interação de Proteínas , Análise de Sequência de RNA
9.
BMC Evol Biol ; 19(1): 173, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462293

RESUMO

BACKGROUND: The annelid anterior central nervous system is often described to consist of a dorsal prostomial brain, consisting of several commissures and connected to the ventral ganglionic nerve cord via circumesophageal connectives. In the light of current molecular phylogenies, our assumptions on the primary design of the nervous system in Annelida has to be reconsidered. For that purpose we provide a detailed investigation of the adult nervous system of Magelonidae - a putatively basally branching annelid family - and studied early stages of the development of the latter. RESULTS: Our comparative investigation using an integrative morphological approach shows that the nervous system of Magelonidae is located inside the epidermis. The brain is composed of an anterior compact neuropil and posteriorly encircles the prostomial coelomic cavities. From the brain two lateral medullary cords branch off which fuse caudally. Prominent brain structures such as nuchal organs, ganglia or mushroom bodies are absent and the entire nervous system is medullary. Our investigations also contradict previous investigations and present an updated view on established assumptions and descriptions. CONCLUSION: The comprehensive dataset presented herein enables a detailed investigation of the magelonid anterior central nervous system for the first time. The data reveal that early in annelid evolution complexity of brains and anterior sensory structures rises. Polymorphic neurons in clusters and distinct brain parts, as well as lateral organs - all of which are not present in outgroup taxa and in the putative magelonid sister group Oweniidae - already evolved in Magelonidae. Commissures inside the brain, ganglia and nuchal organs, however, most likely evolved in the stem lineage of Amphinomidae + Sipuncula and Pleistoannelida (Errantia+ Sedentaria). The investigation demonstrates the necessity to continuously question established descriptions and interpretations of earlier publications and the need for transparent datasets. Our results also hint towards a stronger inclusion of larval morphology and developmental investigations in order to understand adult morphological features, not only in Annelida.


Assuntos
Evolução Biológica , Poliquetos/genética , Animais , Encéfalo/anatomia & histologia , Encéfalo/citologia , Larva/crescimento & desenvolvimento , Sistema Nervoso/anatomia & histologia , Sistema Nervoso/citologia , Filogenia , Poliquetos/anatomia & histologia , Poliquetos/citologia , Poliquetos/crescimento & desenvolvimento
10.
Nat Commun ; 10(1): 3097, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31308381

RESUMO

Dopaminergic neurons in the brain of the Drosophila larva play a key role in mediating reward information to the mushroom bodies during appetitive olfactory learning and memory. Using optogenetic activation of Kenyon cells we provide evidence that recurrent signaling exists between Kenyon cells and dopaminergic neurons of the primary protocerebral anterior (pPAM) cluster. Optogenetic activation of Kenyon cells paired with odor stimulation is sufficient to induce appetitive memory. Simultaneous impairment of the dopaminergic pPAM neurons abolishes appetitive memory expression. Thus, we argue that dopaminergic pPAM neurons mediate reward information to the Kenyon cells, and in turn receive feedback from Kenyon cells. We further show that this feedback signaling is dependent on short neuropeptide F, but not on acetylcholine known to be important for odor-shock memories in adult flies. Our data suggest that recurrent signaling routes within the larval mushroom body circuitry may represent a mechanism subserving memory stabilization.


Assuntos
Encéfalo/fisiologia , Neurônios Dopaminérgicos/fisiologia , Drosophila melanogaster/fisiologia , Memória/fisiologia , Corpos Pedunculados/fisiologia , Recompensa , Acetilcolina/metabolismo , Animais , Apetite/fisiologia , Encéfalo/citologia , Condicionamento Clássico , Retroalimentação Fisiológica , Larva , Modelos Psicológicos , Corpos Pedunculados/citologia , Vias Neurais/fisiologia , Neuropeptídeos/metabolismo , Odorantes , Percepção Olfatória/fisiologia , Optogenética
11.
Genome Biol ; 20(1): 135, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288836

RESUMO

BACKGROUND: The importance of cell type-specific epigenetic variation of non-coding regions in neuropsychiatric disorders is increasingly appreciated, yet data from disease brains are conspicuously lacking. We generate cell type-specific whole-genome methylomes (N = 95) and transcriptomes (N = 89) from neurons and oligodendrocytes obtained from brain tissue of patients with schizophrenia and matched controls. RESULTS: The methylomes of the two cell types are highly distinct, with the majority of differential DNA methylation occurring in non-coding regions. DNA methylation differences between cases and controls are subtle compared to cell type differences, yet robust against permuted data and validated in targeted deep-sequencing analyses. Differential DNA methylation between control and schizophrenia tends to occur in cell type differentially methylated sites, highlighting the significance of cell type-specific epigenetic dysregulation in a complex neuropsychiatric disorder. CONCLUSIONS: Our results provide novel and comprehensive methylome and transcriptome data from distinct cell populations within patient-derived brain tissues. This data clearly demonstrate that cell type epigenetic-differentiated sites are preferentially targeted by disease-associated epigenetic dysregulation. We further show reduced cell type epigenetic distinction in schizophrenia.


Assuntos
Encéfalo/metabolismo , Metilação de DNA , Epigênese Genética , Esquizofrenia/genética , Encéfalo/citologia , Estudos de Casos e Controles , Humanos , Esquizofrenia/metabolismo
12.
Nature ; 571(7764): 205-210, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31270459

RESUMO

The mammalian brain contains neurogenic niches that comprise neural stem cells and other cell types. Neurogenic niches become less functional with age, but how they change during ageing remains unclear. Here we perform single-cell RNA sequencing of young and old neurogenic niches in mice. The analysis of 14,685 single-cell transcriptomes reveals a decrease in activated neural stem cells, changes in endothelial cells and microglia, and an infiltration of T cells in old neurogenic niches. T cells in old brains are clonally expanded and are generally distinct from those in old blood, which suggests that they may experience specific antigens. T cells in old brains also express interferon-γ, and the subset of neural stem cells that has a high interferon response shows decreased proliferation in vivo. We find that T cells can inhibit the proliferation of neural stem cells in co-cultures and in vivo, in part by secreting interferon-γ. Our study reveals an interaction between T cells and neural stem cells in old brains, opening potential avenues through which to counteract age-related decline in brain function.


Assuntos
Envelhecimento/fisiologia , Encéfalo/citologia , Movimento Celular , Células-Tronco Neurais/citologia , Neurogênese , Análise de Célula Única , Nicho de Células-Tronco/fisiologia , Linfócitos T/citologia , Animais , Sangue , Proliferação de Células , Células Clonais/citologia , Técnicas de Cocultura , Células Endoteliais/citologia , Interferon gama/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/citologia , Análise de Sequência de RNA , Transdução de Sinais , Linfócitos T/metabolismo , Transcriptoma/genética
13.
Nature ; 571(7764): 198-204, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31292557

RESUMO

Slow-wave sleep and rapid eye movement (or paradoxical) sleep have been found in mammals, birds and lizards, but it is unclear whether these neuronal signatures are found in non-amniotic vertebrates. Here we develop non-invasive fluorescence-based polysomnography for zebrafish, and show-using unbiased, brain-wide activity recording coupled with assessment of eye movement, muscle dynamics and heart rate-that there are at least two major sleep signatures in zebrafish. These signatures, which we term slow bursting sleep and propagating wave sleep, share commonalities with those of slow-wave sleep and paradoxical or rapid eye movement sleep, respectively. Further, we find that melanin-concentrating hormone signalling (which is involved in mammalian sleep) also regulates propagating wave sleep signatures and the overall amount of sleep in zebrafish, probably via activation of ependymal cells. These observations suggest that common neural signatures of sleep may have emerged in the vertebrate brain over 450 million years ago.


Assuntos
Neurônios/fisiologia , Sono/fisiologia , Peixe-Zebra/fisiologia , Animais , Evolução Biológica , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Epêndima/citologia , Movimentos Oculares , Fluorescência , Frequência Cardíaca , Hipnóticos e Sedativos/farmacologia , Hormônios Hipotalâmicos/metabolismo , Melaninas/metabolismo , Neurônios/efeitos dos fármacos , Pigmentação/fisiologia , Hormônios Hipofisários/metabolismo , Polissonografia/métodos , Sono/efeitos dos fármacos , Privação do Sono/fisiopatologia , Sono REM/efeitos dos fármacos , Sono REM/fisiologia , Sono de Ondas Lentas/efeitos dos fármacos , Sono de Ondas Lentas/fisiologia
14.
Neuron ; 103(4): 583-597.e8, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31272828

RESUMO

Analysis of endogenous protein localization, function, and dynamics is fundamental to the study of all cells, including the diversity of cell types in the brain. However, current approaches are often low throughput and resource intensive. Here, we describe a CRISPR-Cas9-based homology-independent universal genome engineering (HiUGE) method for endogenous protein manipulation that is straightforward, scalable, and highly flexible in terms of genomic target and application. HiUGE employs adeno-associated virus (AAV) vectors of autonomous insertional sequences (payloads) encoding diverse functional modifications that can integrate into virtually any genomic target loci specified by easily assembled gene-specific guide-RNA (GS-gRNA) vectors. We demonstrate that universal HiUGE donors enable rapid alterations of proteins in vitro or in vivo for protein labeling and dynamic visualization, neural-circuit-specific protein modification, subcellular rerouting and sequestration, and truncation-based structure-function analysis. Thus, the "plug-and-play" nature of HiUGE enables high-throughput and modular analysis of mechanisms driving protein functions in cellular neurobiology.


Assuntos
Técnicas de Introdução de Genes/métodos , Genômica/métodos , Engenharia de Proteínas/métodos , Processamento de Proteína Pós-Traducional , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Sistemas CRISPR-Cas , Células Cultivadas , Dependovirus/genética , Edição de Genes/métodos , Vetores Genéticos/genética , Humanos , Imunoquímica/métodos , Inteínas , Camundongos , Mutagênese Insercional , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/genética , Proteômica , RNA Guia/genética , Proteínas Recombinantes de Fusão/genética , Homologia de Sequência do Ácido Nucleico
15.
Nat Commun ; 10(1): 2845, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253782

RESUMO

A puzzle for neuroscience-and robotics-is how insects achieve surprisingly complex behaviours with such tiny brains. One example is depth perception via binocular stereopsis in the praying mantis, a predatory insect. Praying mantids use stereopsis, the computation of distances from disparities between the two retinal images, to trigger a raptorial strike of their forelegs when prey is within reach. The neuronal basis of this ability is entirely unknown. Here we show the first evidence that individual neurons in the praying mantis brain are tuned to specific disparities and eccentricities, and thus locations in 3D-space. Like disparity-tuned cortical cells in vertebrates, the responses of these mantis neurons are consistent with linear summation of binocular inputs followed by an output nonlinearity. Our study not only proves the existence of disparity sensitive neurons in an insect brain, it also reveals feedback connections hitherto undiscovered in any animal species.


Assuntos
Encéfalo/fisiologia , Percepção de Profundidade/fisiologia , Mantódeos/fisiologia , Neurônios/fisiologia , Animais , Encéfalo/citologia , Visão Binocular/fisiologia
16.
Nat Commun ; 10(1): 2851, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253786

RESUMO

Male and female brains differ significantly in both health and disease, and yet the female brain has been understudied. Sex-hormone fluctuations make the female brain particularly dynamic and are likely to confer female-specific risks for neuropsychiatric disorders. The molecular mechanisms underlying the dynamic nature of the female brain structure and function are unknown. Here we show that neuronal chromatin organization in the female ventral hippocampus of mouse fluctuates with the oestrous cycle. We find chromatin organizational changes associated with the transcriptional activity of genes important for neuronal function and behaviour. We link these chromatin dynamics to variation in anxiety-related behaviour and brain structure. Our findings implicate an immediate-early gene product, Egr1, as part of the mechanism mediating oestrous cycle-dependent chromatin and transcriptional changes. This study reveals extreme, sex-specific dynamism of the neuronal epigenome, and establishes a foundation for the development of sex-specific treatments for disorders such as anxiety and depression.


Assuntos
Encéfalo/fisiologia , Cromatina/fisiologia , Ciclo Estral/fisiologia , Neurônios/fisiologia , Animais , Comportamento Animal , Encéfalo/citologia , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Epigenômica , Estradiol/metabolismo , Feminino , Regulação da Expressão Gênica/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/citologia , Progesterona/metabolismo , Ligação Proteica , RNA/genética , RNA/metabolismo
17.
Nat Commun ; 10(1): 2817, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31249304

RESUMO

Sufficient vascular supply is indispensable for brain development and function, whereas dysfunctional blood vessels are associated with human diseases such as vascular malformations, stroke or neurodegeneration. Pericytes are capillary-associated mesenchymal cells that limit vascular permeability and protect the brain by preserving blood-brain barrier integrity. Loss of pericytes has been linked to neurodegenerative changes in genetically modified mice. Here, we report that postnatal inactivation of the Rbpj gene, encoding the transcription factor RBPJ, leads to alteration of cell identity markers in brain pericytes, increases local TGFß signalling, and triggers profound changes in endothelial behaviour. These changes, which are not mimicked by pericyte ablation, imperil vascular stability and induce the acquisition of pathological landmarks associated with cerebral cavernous malformations. In adult mice, loss of Rbpj results in bigger stroke lesions upon ischemic insult. We propose that brain pericytes can acquire deleterious properties that actively enhance vascular lesion formation and promote pathogenic processes.


Assuntos
Encéfalo/metabolismo , Hemangioma Cavernoso do Sistema Nervoso Central/metabolismo , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/deficiência , Pericitos/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/citologia , Progressão da Doença , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Humanos , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Masculino , Camundongos Knockout
18.
Neuron ; 103(1): 21-38.e5, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31147152

RESUMO

Understanding brain-wide neuronal dynamics requires a detailed map of the underlying circuit architecture. We built an interactive cellular-resolution atlas of the zebrafish brain at 6 days post-fertilization (dpf) based on the reconstructions of over 2,000 individually GFP-labeled neurons. We clustered our dataset in "morphotypes," establishing a unique database of quantitatively described neuronal morphologies together with their spatial coordinates in vivo. Over 100 transgene expression patterns were imaged separately and co-registered with the single-neuron atlas. By annotating 72 non-overlapping brain regions, we generated from our dataset an inter-areal wiring diagram of the larval brain, which serves as ground truth for synapse-scale, electron microscopic reconstructions. Interrogating our atlas by "virtual tract tracing" has already revealed previously unknown wiring principles in the tectum and the cerebellum. In conclusion, we present here an evolving computational resource and visualization tool, which will be essential to map function to structure in a vertebrate brain. VIDEO ABSTRACT.


Assuntos
Atlas como Assunto , Encéfalo/anatomia & histologia , Encéfalo/citologia , Peixe-Zebra/anatomia & histologia , Animais , Encéfalo/ultraestrutura , Mapeamento Encefálico , Cerebelo/anatomia & histologia , Conectoma , Expressão Gênica , Proteínas de Fluorescência Verde , Larva/anatomia & histologia , Larva/citologia , Neurônios/ultraestrutura , Transgenes , Vias Visuais/anatomia & histologia
19.
Neuron ; 103(2): 217-234.e4, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31171447

RESUMO

Synapses are fundamental information-processing units of the brain, and synaptic dysregulation is central to many brain disorders ("synaptopathies"). However, systematic annotation of synaptic genes and ontology of synaptic processes are currently lacking. We established SynGO, an interactive knowledge base that accumulates available research about synapse biology using Gene Ontology (GO) annotations to novel ontology terms: 87 synaptic locations and 179 synaptic processes. SynGO annotations are exclusively based on published, expert-curated evidence. Using 2,922 annotations for 1,112 genes, we show that synaptic genes are exceptionally well conserved and less tolerant to mutations than other genes. Many SynGO terms are significantly overrepresented among gene variations associated with intelligence, educational attainment, ADHD, autism, and bipolar disorder and among de novo variants associated with neurodevelopmental disorders, including schizophrenia. SynGO is a public, universal reference for synapse research and an online analysis platform for interpretation of large-scale -omics data (https://syngoportal.org and http://geneontology.org).


Assuntos
Encéfalo/citologia , Ontologia Genética , Proteômica , Software , Sinapses/fisiologia , Animais , Encéfalo/fisiologia , Bases de Dados Genéticas , Humanos , Bases de Conhecimento , Potenciais Sinápticos/fisiologia , Sinaptossomos
20.
Neuron ; 103(3): 395-411.e5, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31201122

RESUMO

Computational models are powerful tools for exploring the properties of complex biological systems. In neuroscience, data-driven models of neural circuits that span multiple scales are increasingly being used to understand brain function in health and disease. But their adoption and reuse has been limited by the specialist knowledge required to evaluate and use them. To address this, we have developed Open Source Brain, a platform for sharing, viewing, analyzing, and simulating standardized models from different brain regions and species. Model structure and parameters can be automatically visualized and their dynamical properties explored through browser-based simulations. Infrastructure and tools for collaborative interaction, development, and testing are also provided. We demonstrate how existing components can be reused by constructing new models of inhibition-stabilized cortical networks that match recent experimental results. These features of Open Source Brain improve the accessibility, transparency, and reproducibility of models and facilitate their reuse by the wider community.


Assuntos
Encéfalo/fisiologia , Biologia Computacional/normas , Simulação por Computador , Modelos Neurológicos , Neurônios/fisiologia , Encéfalo/citologia , Biologia Computacional/métodos , Humanos , Internet , Redes Neurais (Computação) , Sistemas On-Line
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